Rabies Therapeutics

Although rabies is reputed to be 100% fatal once the symptomatic phase is reached, in recent years an increased interest has arisen for therapeutic approaches. The “Milwaukee” protocol successfully applied to a rabid patient in 2005 has revitalized interest (although highly criticized by some investigators) in the rabies community. Most approaches still remain at a very early and conceptual stage of development. Rabies and its long incubation period is obviously an excellent target to develop an antiviral, even if its status as a neglected disease and its neurotropism are two economical and physiological obstacles, respectively, from this perspective. This review presents the empirical arsenal of substances having shown “some” anti-rabies viral (RABV) activity, then describes two complementary strategies that are currently elaborated for the rationale development of antivirals against RABV and other lyssaviruses: (1) a cognitive approach by destabilization of the known functional interactions between viral components, and (2) a random approach by high-throughput screening of highly diverse libraries of molecules using functional tests.